Complete quantum control of exciton qubits bound to isoelectronic centres.

In recent years, impressive demonstrations related to quantum information processing have been realized. The scalability of quantum interactions between arbitrary qubits within an array remains however a significant hurdle to the practical realization of a quantum computer. Among the proposed ideas to achieve fully scalable quantum processing, the use of photons is appealing because they can mediate long-range quantum interactions and could serve as buses to build quantum networks. Quantum dots or nitrogen-vacancy centres in diamond can be coupled to light, but the former system lacks optical homogeneity while the latter suffers from a low dipole moment, rendering their large-scale interconnection challenging. Here, through the complete quantum control of exciton qubits, we demonstrate that nitrogen isoelectronic centres in GaAs combine both the uniformity and predictability of atomic defects and the dipole moment of semiconductor quantum dots. This establishes isoelectronic centres as a promising platform for quantum information processing.

Strong coupling in the sub-wavelength limit using metamaterial nanocavities.

The interaction between cavity modes and optical transitions leads to new coupled light-matter states in which the energy is periodically exchanged between the matter states and the optical mode. Here we present experimental evidence of optical strong coupling between modes of individual sub-wavelength metamaterial nanocavities and engineered optical transitions in semiconductor heterostructures. We show that this behaviour is generic by extending the results from the mid-infrared (~10 µm) to the near-infrared (~1.5 µm). Using mid-infrared structures, we demonstrate that the light-matter coupling occurs at the single resonator level and with extremely small interaction volumes. We calculate a mode volume of 4.9 × 10(-4) (λ/n)(3) from which we infer that only ~2,400 electrons per resonator participate in this energy exchange process.

Monolithic metallic nanocavities for strong light-matter interaction to quantum-well intersubband excitations.

We present the design, realization and characterization of strong coupling between an intersubband transition and a monolithic metamaterial nanocavity in the mid-infrared spectral range. We use a ground plane in conjunction with a planar metamaterial resonator for full three-dimensional confinement of the optical mode. This reduces the mode volume by a factor of 1.9 compared to a conventional metamaterial resonator while maintaining the same Rabi frequency. The conductive ground plane is implemented using a highly doped n+ layer which allows us to integrate it monolithically into the device and simplify fabrication.

Removal of nonspecific binding proteins from cell and tissue extracts using 2-aminobenzimidazole-tethered affinity resin.

Cellular drug target identification through affinity chromatography is often hindered by the quantity of nonspecific binders, such as cytoskeletal and heat shock proteins. Thus, we prepared a 2-aminobenzimidazole-tethered depletion resin designed for removal of these proteins, and tested it on human lung carcinoma cell and rat tissue extracts. Column-bound proteins were identified by two-dimensional gel electrophoresis and MS. Among others, tubulins, actins and heat shock proteins were successfully depleted. Due to the reduction of these highly abundant proteins detection of potential drug targets is considerably facilitated in the pre-purified samples.

Optical spectroscopy of single impurity centers in semiconductors.

Using optical spectroscopy with diffraction limited spatial resolution, the possibility of measuring the luminescence from single impurity centers in a semiconductor is demonstrated. Selectively studying individual centers that are formed by two neighboring nitrogen atoms in GaAs makes it possible to unveil their otherwise concealed polarization anisotropy, analyze their selection rules, identify their particular configuration, map their spatial distribution, and demonstrate the presence of a diversity of local environments. Circumventing the limitation imposed by ensemble averaging and the ability to discriminate the individual electronic responses from discrete emitters provides an unprecedented perspective on the nanoscience of impurities.

Inhibition of the death receptor pathway by cFLIP confers partial engraftment of MHC class I-deficient stem cells and reduces tumor clearance in perforin-deficient mice.

NK cells mediate acute rejection of MHC class I-deficient bone marrow cell (BMC) grafts. However, the exact cytotoxic mechanisms of NK cells during acute BMC graft rejection are not well defined. Although the granule exocytosis pathway plays a major role in NK cell-mediated rejection, alternative perforin-independent mechanisms also exist. By analyzing the anti-apoptotic effects of cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein (cFLIP) overexpression, we investigated the possible role of death receptor-induced apoptosis in NK cell-mediated cytotoxicity. In the absence of perforin, we found that cFLIP overexpression reduces lysis of tumor cells by NK cells in vitro and in vivo. In addition, perforin-deficient NK cells were impaired in their ability to acutely reject cFLIP-overexpressing TAP-1 knockout stem cells. These results emphasize the importance of NK cell death receptor-mediated killing during BMC grafts in the absence of perforin.

Detection of deep venous thrombosis by DMP 444, a platelet IIb/IIIa antagonist: a preliminary report.

BACKGROUND: We report a method for detection of deep venous thrombosis with a technetium 99m-labeled peptide (DMP 444). The N-methyl-arginine-glycine-aspartic acid sequence on DMP 444 binds the glycoprotein IIb/IIIa receptor on activated platelets (inhibition constant [IC50] for fibrinogen binding = 6 nmol/L). METHODS: DMP 444 (23 to 27 mCi) was injected into 11 patients with clinical suspicion of deep venous thrombosis, diagnostic confirmation by ultrasound, and a positive D-dimer test result. Planar images in the anterior and posterior projections were obtained at 10 to 40 minutes, 50 to 80 minutes, and 120 to 150 minutes after injection. RESULTS: No clinically significant adverse effects were noted after DMP 444 administration. One patient (excluded from the analysis) withdrew consent, so image acquisition was not complete. By 10 to 40 minutes after injection, 8 of 10 patients demonstrated an area of increased activity that was clearly related to the abnormality noted on ultrasound. Most patients were taking warfarin (Coumadin) and heparin (n = 8) or heparin (n = 1) and warfarin (n = 1) alone at the time of the imaging. The average time from onset of symptoms to injection of DMP 444 was 5 days (range 1 to 18 days). CONCLUSION: These preliminary human studies indicate that DMP 444 is safe and may be of value in the diagnosis of deep venous thrombosis.

Differentiation of NK1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells.

To delineate factors involved in NK cell development, we established an in vitro system in which lineage marker (Lin)-, c-kit+, Sca2+ bone marrow cells differentiate into lytic NK1.1+ but Ly49- cells upon culture in IL-7, stem cell factor (SCF), and flt3 ligand (flt3L), followed by IL-15 alone. A comparison of the ability of IL-7, SCF, and flt3L to generate IL-15-responsive precursors suggested that NK progenitors express the receptor for flt3L. In support of this, when Lin-, c-kit+, flt3+ or Lin-, c-kit+, flt3- progenitors were utilized, 3-fold more NK cells arose from the flt3+ than from the flt3- progenitors. Furthermore, NK cells that arose from flt3- progenitors showed an immature NK1.1dim, CD2-, c-kit+ phenotype as compared with the more mature NK1.1bright, CD2+/-, c-kit- phenotype displayed by NK cells derived from flt3+ progenitors. Both progenitors, however, gave rise to NK cells that were Ly49 negative. To test the hypothesis that additional marrow-derived signals are necessary for Ly49 expression on developing NK cells, flt3+ progenitors were grown in IL-7, SCF, and flt3L followed by culture with IL-15 and a marrow-derived stromal cell line. Expression of Ly49 molecules, including those of which the MHC class I ligands were expressed on the stromal or progenitor cells, as well as others of which the known ligands were absent, was induced within 6-13 days. Thus, we have established an in vitro system in which Ly49 expression on developing NK cells can be analyzed and possibly experimentally manipulated.

Induction and characterization of human glioma clones with different radiosensitivities.

To facilitate investigation of the molecular mechanisms of tumor cell radiosensitivities, we have generated a set of clones with different radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and then irradiating these cells with increasing doses of x-rays. About half of the clones displayed different radiosensitivities than the parent cells. We selected one of the most sensitive clones (X3i) and one of the most resistant clones (Y6) for further study. Isoeffective doses for these two clones differed by about a factor of 1.7; the relative radiosensitivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ significantly in either the induction or repair of radiation-induced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay and micronucleus formation were similar in both clones. However, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency assay.

Natural killer cell differentiation: insights from knockout and transgenic mouse models and in vitro systems.

In the last few years, the routine development of knockout and transgenic mice and the ease with which rare progenitor populations can be isolated from hematopoietic organs and cultured in vitro has facilitated significant advances in understanding the lineage and development of natural killer (NK) cells. Fluorescence-activated cell sorter analyses have identified a common lymphoid progenitor capable of giving rise to NK, T, and B cells, confirming the lymphoid origin of NK cells. Knockout and transgenic mouse models have pointed to an absolutely critical role for signals sent through the interleukin (IL)-2/15 receptor beta (CD122) chain and common gamma (gamma c) chain for NK development. Such signals are likely relayed inside the cell by the tyrosine kinase Jak3, which associates with gamma c. Recently developed IL-15 and IL-15 receptor alpha knockout mice have pinpointed IL-15 as the mediator of this signal. Other mouse models have indicated an unexpected role for flt3 ligand in early NK-cell development as well as minor roles for stem cell factor and IL-7 in expanding NK-cell progenitor numbers. Finally, in vitro culture systems have proven useful in identifying the point in NK development at which each of these signals is critical.

Adenosine deaminase activity in blood of patients with stable angina pectoris.

The activity of adenosine deaminases (EC.3.5.4.4) in granulocytes and lymphocytes of patients with stable angina pectoris was lower by about 27% and 24%, respectively as compared with control group, whereas these values in erythrocytes and blood plasma were at the normal level.

5'-nucleotidase and adenosine deaminase activities in blood of patients with unstable angina pectoris.

During ischaemia and hypoxia adenosine is released from cardiac cells. Adenosine is the end product of 5'-nucleotidase activity. We were interested in how this enzyme activity in plasma of patients with unstable angina pectoris, causes short-term ischaemia. 5'-Nucleotidase activity in plasma was determined using a standard diagnostic kit from Sigma. Furthermore, we studied the activity of adenosine deaminase in plasma, granulocytes, lymphocytes and erythrocytes by the methods of Hopkinson [1]. It was found that 5'-nucleotidase activity was increased by about 43% in plasma. The activity of adenosine deaminase (ADA) in plasma increased by 6%, but in granulocytes, lymphocytes and erythrocytes decreased by about 24, 19 and 10.6%, respectively. We concluded that a large increase in 5'-nucleotidase activity may be caused by activation of 5'-ectonucleotidase in blood cells by ischaemia. However, the decrease in ADA activity in blood cells may be associate with the adenosine metabolism.

Red blood cell superoxide dismutase and catalase activities in patients suffering from multiple sclerosis treated with adrenocorticotropic hormone.

The purpose of this study was to determine superoxide dismutase (SOD) and catalase (CAT) activities in erythrocytes of patients with multiple sclerosis treated with ACTH. SOD activity in hemolysates was determined according to the method of Misra and Fridovich and calculated as units per gram of hemoglobin (Hb). CAT activity in hemolysates was determined with Beers and Sizer's method and expressed in IU/g Hb. SOD activity in control group was (1.61 +/- 0.45) x 10(3) U/g Hb whereas, the activity of CAT amounted to (5.88 +/- 1.36) x 10(4) U/g Hb. Before the treatment, SOD activity was decreased by approximately 20% ((1.25 +/- 0.25) x 10(3) U/g Hb) while that of CAT-by about 7.7% ((5.43 +/- 0.68) x 10(4) U/g Hb) in comparison to the normal control. After treatment with ACTH, activity of both enzymes increased: SOD-by about 34.4% to (1.68 +/- 0.38) x 10(3) U/g Hb and CAT-by about 7% to (6.29 +/- 0.55) x 10(4) U/g Hb. Results of investigations showed that ACTH caused an increase in CAT and SOD activities in erythrocytes of patients after three-week treatment.

Activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone.

Adenosine deaminase (ADA) activity was studied in red blood cells of patients suffering from multiple sclerosis treated with adrenocorticotropic hormone (ACTH). ADA activity in hemolysates was determined according to the method of Hopkinson and calculated as units per g of hemoglobin. Activity of adenosine deaminase in healthy subjects was 0.871 +/- 0.251 U/g Hb. In patients with multiple sclerosis, before treatment ADA activity was 0.765 +/- 0.131 U/g Hb and was about 15.2% lower than in the control group (p < 0.02). After treatment with ACTH, ADA activity increased to 1.005 +/- 0.211 U/g Hb (p < 0.001). We have suggested that increased activity of adenosine deaminase in red blood cells of patients suffering from multiple sclerosis after treatment with ACTH is caused by diminution of superoxide generation, and therefore its sparing effect on cell membrane and enzyme is connected with membranes.

Superoxide dismutase and catalase activity in psoriatic patients treated topically with ointment containing 2-chloroethyl-3-chloropropyl sulfide.

The purpose of this study was to determine dismutase and catalase activities in erythrocytes of psoriatic patients with psoriasis vulgaris topically treated with an ointment (in accordance with recommendations of the Helsinki Declaration), in which 2-chloroethyl-3-chloropropyl sulfide (CLEPS) is an active compound. SOD activity in hemolysates was determined according to the method of Misra and Fridovich [12] and calculated as units per g of hemoglobin. CAT activity in hemolysates was determined by Beers and Sizer method [2] and expressed in U/g Hb. SOD activity in the control group was 1.61 +/- 0.48 U/g Hb x 10(3). However, the activity of CAT was 5.72 +/- 1.17 U/g Hb x 10(4). Before treatment SOD activity was decreased by ca. 22.5% (1.25 +/- 0.53 U/g Hb x 10(3)) while that of CAT by about 7% (5.30 +/- 1.41 U/g Hb x 10(4)), in comparison with the normal control. After treatment with the ointment, activity of both enzymes increased by about 18% to 1.55 x 10(3) U/g Hb and by about 16.5% to 6.25 x 10(4) U/g Hb, respectively. The results of our investigations showed that the ointment (containing mustard gas derivative) applied on psoriatic skin, causes increased of SOD and CAT activity in erythrocytes after regression of psoriatic lesions and treatment termination.